PROJECT SUMMARY Extant animal and human data show that ovarian hormones are critical neurobiological risk factors for binge eating in women. Natural increases in these hormones across the menstrual cycle substantially increase risk for binge eating via hormonally induced increases in genetic risk. These data have significantly advanced etiological models and our understanding of the female predominance in eating disorder risk. However, this increased knowledge comes with an urgent public health responsibility. In the US today, 1 in 3 women take contraceptives that contain combinations of hormones that mimic the riskiest milieus for binge eating (i.e., combined oral contraceptives (COCs) containing both estrogen and progesterone).The relatively commonplace prescription of COCs may substantially increase risk for binge eating in women, particularly in those who are genetically vulnerable to eating disorders. This possibility underscores the urgent need to examine COC effects on binge eating to inform women's health practices and avert a potentially dangerous (and chronic) path toward eating disorders in unsuspecting young women. The goal of the proposed project is to use a multi- method (behavioral genetic, neuroendocrine), longitudinal twin study to document the effects of COCs on phenotypic and genetic risk for binge eating in women. If COCs increase phenotypic risk for binge eating in women, then there should be significantly higher rates of binge eating in twins using COCs than their non- using co-twins (a population-level, between-subject effect) and substantial increases in binge eating when COC users transition from inactive to active pills (an individual-level, within-subject effect). Moreover, if COCs influence binge eating through genetic mechanisms, then there should be significantly increased genetic risk in twins taking COCs (a population-level, between-subject effect) and substantial increases in genetic effects when COC users transition from inactive to active pills (an individual-level, within-subject effect). We will examine all of these hypotheses in a large sample of female twins (N = 1,000) assessed daily for 45 days using multiple measures of binge eating and related phenotypes. Notably, the proposed project would directly address NIH directives to enhance Rigor and Reproducibility through its validation of cross-sectional findings (e.g., increased binge eating in COC twins vs. their non-using co-twins) with longitudinal data (i.e., increased binge eating when transitioning from inactive to active pills) within a twin study design that substantially minimizes confounders and selection factors into COC use. The inferential power gained from these multi-level analyses has the potential to significantly advance public health policy and necessitate a re-thinking of basic assumptions about COC prescriptions and use. The clinical implications of our findings run the gamut from requiring physicians to screen for personal and family histories of eating disorders (an uncommon practice) to the selection of alternative contraceptives that are less risky for women.